Addison's disease test: how adrenal insufficiency is diagnosed

Addison's disease is diagnosed with blood tests arranged by a doctor. The usual first step is a blood cortisol taken between 8 and 9am, when levels should be near their daily peak. A low or borderline result leads to a short Synacthen test in hospital, which shows whether the adrenal glands can raise cortisol when stimulated.¹² The Endocrine Society calls the Synacthen test the gold standard for diagnosing primary adrenal insufficiency.³ No home test, hair included, can diagnose or rule out Addison's disease. And anyone who may be having an adrenal crisis needs emergency treatment first: the tests can wait.³

What is Addison's disease?

Addison's disease, or primary adrenal insufficiency, happens when the adrenal cortex, the outer layer of the adrenal glands where cortisol is made, is destroyed. In Western countries about 90 per cent of cases are autoimmune, caused by the immune system attacking the glands.² The damage can also affect aldosterone, a hormone that helps control salt balance, which is why the Endocrine Society recommends measuring it alongside a related hormone, renin.³

It is rare. NICE puts its prevalence at 100 to 220 per million people in Western Europe and the US, with 4.4 to 6.2 new cases per million a year in Europe. In the UK about 9,000 people have the diagnosis and about 320 are diagnosed each year.² It most often starts between the ages of 30 and 50, and more women than men are affected.²

Addison's is one form of adrenal insufficiency. The others are secondary adrenal insufficiency, where the pituitary gland does not send enough ACTH, the hormone that tells the adrenal glands to make cortisol,⁴ and glucocorticoid-induced adrenal insufficiency, which follows long-term steroid medicine and is a risk for the at least 1 per cent of the population who take it.⁵ The tests overlap, but this guide focuses on Addison's. The symptoms, such as extreme tiredness, weight loss, dizziness on standing, salt craving and darker skin, are covered in low cortisol symptoms.⁶

Step one: an 8 to 9am cortisol blood test

Cortisol peaks at around 8.30 in the morning,⁷ so a sample taken between 8 and 9am catches the adrenal glands at their busiest. For people aged 16 and over, NICE uses these thresholds, which apply to modern immunoassays:¹

NICE's summary for GPs adds a level of urgency: below 100 nmol/L, adrenal insufficiency is highly likely and the person should be admitted to hospital.² If your result is in µg/dL, our cortisol converter changes the units.

Several things can make a morning cortisol misleading:

• Oral oestrogen, in many contraceptive pills and some HRT, makes total blood cortisol read falsely high, so NICE advises stopping it for 6 weeks before the test.¹
• Steroid medicines, including inhaled, injected or skin preparations at doses equal to or above the body's own output, can give a low result. NICE advises waiting 4 weeks after a steroid injection into a muscle or joint.¹ One NHS laboratory states that a cortisol taken while on steroid treatment, or at a random time of day, cannot be interpreted.⁸
• Shift work makes it unclear when to test, so NICE's GP guidance advises asking a specialist before testing shift workers.²

Doctors also measure ACTH. In someone with confirmed low cortisol, an ACTH level more than twice the upper limit of normal is consistent with primary adrenal insufficiency, which helps separate Addison's from a pituitary cause.³

Step two: the short Synacthen test

The Synacthen test, also called the ACTH stimulation test, checks how the adrenal glands respond when pushed. A blood sample is taken, you are given an injection of 250 µg of tetracosactide, a synthetic form of ACTH, and cortisol is measured again 30 or 60 minutes later. Healthy adrenal glands raise cortisol above about 500 to 550 nmol/L; a peak below 500 nmol/L is diagnostic of primary adrenal insufficiency, although the exact cut-off depends on the laboratory's method.² NICE's GP guidance says the diagnosis is confirmed in hospital with this test.²

The Endocrine Society describes the short test as the gold standard, with a peak below 500 nmol/L (18 µg/dL) at 30 or 60 minutes indicating adrenal insufficiency, and a pooled sensitivity of 92 per cent.³ The cut-off is shifting as laboratory methods change, because newer, more specific methods read lower:

• MedlinePlus gives a normal response as above 15 to 16 µg/dL (430 to 450 nmol/L), depending on the method and the ACTH dose.⁹
• A 2021 study recommended a 30-minute cut-off of 14 to 15 µg/dL with newer specific immunoassays and LC-MS/MS, instead of the historical 18 µg/dL.¹⁰
• Using LC-MS/MS in 138 healthy people, a 2018 study set cut-offs of 412 nmol/L at 30 minutes and 485 nmol/L at 60 minutes. With these, 13 of 60 people (22 per cent) classed as having adrenal insufficiency by conventional criteria had a normal result.¹¹
• Another study found the 30-minute lower limit ranged from 420 to 574 nmol/L depending on the method, and that women taking the combined pill need separate limits.¹²

The practical point is that your result is read against your own laboratory's cut-off, not a number from elsewhere. See the Synacthen test for how to prepare and what the day involves.

Adrenal crisis and sick-day rules

An adrenal crisis is a sudden, life-threatening shortage of cortisol. The NHS advises calling 999 (911 in the US) if someone with Addison's disease suddenly gets worse or has a fast heart rate; severe dizziness, especially on standing; severe pain in the tummy or side; muscle weakness, pain or spasms; a headache that will not go away; nausea or vomiting; drowsiness, irritability or confusion; or a seizure or loss of consciousness. If they have an emergency hydrocortisone injection, give it, and still call 999.⁶

Treatment comes before tests. The Endocrine Society recommends immediate intravenous hydrocortisone for anyone with severe symptoms or a suspected crisis, and says treatment should not be delayed while waiting for a Synacthen test.³ UK emergency guidance for adults is an immediate 100 mg of hydrocortisone, then 200 mg over 24 hours, with rapid fluids.¹³ NICE's GP guidance gives 50 mg for children aged 1 to 5 and 25 mg for babies under 1, with emergency admission.² NICE also asks doctors to suspect a crisis in anyone critically unwell with low blood pressure, darker skin, low sodium, low blood sugar, shock or collapse, or an illness that is not responding to treatment.¹

Once diagnosed, people with Addison's learn sick-day rules to prevent a crisis. The Society for Endocrinology advises doubling the daily tablet dose during an illness with a fever that needs bed rest or antibiotics, and giving the steroid by injection during prolonged vomiting or diarrhoea, before a colonoscopy, and with injury or surgery.¹³ The Endocrine Society recommends that everyone with the condition carries a steroid emergency card and medical alert identification, and has an injection kit they have been taught to use.³

Why hair cortisol has no role in diagnosis

Hair cortisol shows average cortisol over months, and it has been studied in people with adrenal insufficiency, but not as a diagnostic test. Neither the Endocrine Society guideline nor NICE includes it.³¹ It cannot do the job for three reasons:

• The diagnosis depends on a response, not an average. The Synacthen test asks whether the adrenal glands can raise cortisol when stimulated.² A resting average, from any sample, cannot answer that.
• Hair looks backwards. The centimetre nearest the scalp reflects hair formed roughly 1.3 to 2.2 months before the cut,¹⁴ so it cannot show whether someone is short of cortisol now, which is what matters in an emergency.
• There are no diagnostic cut-offs. Healthy hair cortisol values differ more than tenfold between laboratories,¹⁵¹⁶ and hair cortisol has no agreed reference range or guideline threshold.¹⁷

Where hair has been studied is in people already diagnosed and taking hydrocortisone. Hair cortisol rose with the hydrocortisone dose in two studies,¹⁸¹⁹ and a 2026 study found lower values in patients judged under-treated and higher values in those judged over-treated, though the study was cross-sectional and the authors called for prospective research on adjusting doses.²⁰ For now the Endocrine Society suggests monitoring replacement by clinical assessment, such as weight, blood pressure on standing, energy levels and signs of too much steroid, and suggests against using hormone tests for this; NICE also advises monitoring signs and symptoms.³¹

If you are worried about low cortisol, the right route is a GP and, if needed, an endocrinologist. Our guide to getting a cortisol test from your doctor explains how to ask, and adrenal fatigue explains why tests sold for that idea are not a substitute.